Candidate: Dr. Grogg has a strong background in physics, with a Ph.D. in experimental high energy physics. Seeking a research opportunity that would potentially have more practical applications, she began working as a research fellow at Massachusetts General Hospital (MGH). She has been investigating the use of positron emission tomography (PET) in the verification of dose delivery for proton therapy. One of her immediate goals is to use advanced imaging techniques to improve the planning and verification stages of proton therapy, as a means for increasing precision and reducing uncertainty. By doing so, patients will receive the prescribed doses to their tumors while avoiding damage to healthy tissue, thus experiencing fewer side effects. Her long- term goal is to establish a planning system that will reduce uncertainty in dose range to below 2 mm, as well as a clinically viable verification method that will identify sub-optimal deliveries and give feedback for improvement. Environment: MGH provides an ideal setting for conducting research in both medical imaging and proton therapy because of the multiple state-of-the art imaging systems available, including the first ever mobile PET/CT unit. The Burr Proton Center (BPC) provides a broad range of expertise in proton therapy planning, quality assurance, and treatment delivery. The Nuclear Medicine and Molecular Imaging division (NMMI) provides access to a global shared memory supercomputer ideal for the Monte Carlo (MC) simulations on which proton therapy relies. NMMI is also home to many experts in both PET and CT imaging who will provide their knowledge and expertise to this project. The scientists from both centers will be available for consultations and mentoring, when needed, on this project. Research plan: The following proposal seeks to develop two complementary imaging modalities, PET and CT, in order to enhance proton therapy planning and to integrate in vivo verification of proton dose delivery into the clinical workflow. While protons have a finite range in matter, stopping within a target and delivering lower dose to healthy tissue, there is an uncertainty of up to 4.6%+1.2 mm in the calculation of the proton range when planning a treatment, potentially leading to under-doses to tumors or overdoses to healthy tissue. Dual-energy CT (DECT) is proposed as an effective solution for reducing the range uncertainty in treatment planning by providing higher quality information about the tissue being irradiated, and thus a more accurate expected proton range. For verification, in-room PET images are compared to MC simulations of the expected PET images to ascertain the difference between the planned and delivered ranges. DECT will be used to improve the MC simulations, both for range determination and for calculations of PET isotope production. Additionally, dynamic PET imaging and estimations of radioactivity clearance rates will be explored for the potential to identify biological changes in response to treatment.